4.8 Article

Membrane fusion and drug delivery with carbon nanotube porins

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2016974118

关键词

carbon nanotube porins; membrane fusion; drug delivery; liposomes

资金

  1. US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [SCW097217]
  2. Division of Materials Research of the National Science Foundation [1710211]
  3. Lawrence Livermore National Laboratory (LLNL) Laboratory Directed Research and Development (LDRD) Program [18ERD011]
  4. US Department of Energy [DEAC5207NA27344]
  5. Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DEAC0205CH11231]
  6. Max Planck Society
  7. LandesOffensive zur Entwicklung Wissenschaftlichodkonomischer Exzellenz DynaMem program of the state of Hesse
  8. Engineering and Physical Sciences Research Council [EP/R004072/1]
  9. Direct For Mathematical & Physical Scien [1710211] Funding Source: National Science Foundation
  10. Division Of Materials Research [1710211] Funding Source: National Science Foundation
  11. EPSRC [EP/R004072/1] Funding Source: UKRI

向作者/读者索取更多资源

Liposomes with carbon nanotube porins (CNTPs) on their membranes have been found to be efficient vehicles for direct cytoplasmic drug delivery, enhancing the killing effect of anticancer drugs on cancer cells. This research opens up new possibilities for designing more efficient drug delivery carriers.
Drug delivery mitigates toxic side effects and poor pharmacokinetics of life-saving therapeutics and enhances treatment efficacy. However, direct cytoplasmic delivery of drugs and vaccines into cells has remained out of reach. We find that liposomes studded with 0.8-nm-wide carbon nanotube porins (CNTPs) function as efficient vehicles for direct cytoplasmic drug delivery by facilitating fusion of lipid membranes and complete mixing of the membrane material and vesicle interior content. Fusion kinetics data and coarse-grained molecular dynamics simulations reveal an unusual mechanism where CNTP dimers tether the vesicles, pull the membranes into proximity, and then fuse their outer and inner leaflets. Liposomes containing CNTPs in their membranes and loaded with an anticancer drug, doxorubicin, were effective in delivering the drug to cancer cells, killing up to 90% of them. Our results open an avenue for designing efficient drug delivery carriers compatible with a wide range of therapeutics.

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